Multiple Sclerosis impact on employment and income in New Zealand.

BACKGROUND AND OBJECTIVES: We investigated the demographic, social and clinical characteristics associated with employment status and income for people with multiple sclerosis (MS) in New Zealand (NZ). METHODS: The NZ National MS Prevalence study included all persons resident in NZ on census day 2006 diagnosed with MS (96.7% coverage). Factors associated with employment and income status among the working age population (25-64 years) were identified by linear regression. RESULTS: Over 90% of working age people with MS (n=1727) had a work history, but 54% were not working. Work loss occurred early in the disease course, and at low disability (P<.001). Advancing age, progressive disease, longer disease duration, higher disability levels, partner loss and lower education were associated with work loss (P<.001). Working age people with MS had lower income than the NZ population (P<.0001). Higher qualifications yielded no additional income for MS females and about half the additional income for MS males (P<.0001). CONCLUSIONS: MS profoundly reduces employment and income early in the disease course, and at low levels of disability, however, unemployment is not entirely accounted for by clinical, social and demographic factors. These findings suggest social supports should be explored early in the disease course to reduce loss of income and unemployment for people with MS.

Genetics of schizophrenia in the South African Xhosa.

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide.

Scales for rating impairment in multiple sclerosis: a critique.

We reviewed scales proposed over the past 35 years for the rating of neurologic impairment in MS. We focused on the Expanded Disability Status Scale (EDSS) which has been recommended as the most useful scale for rating impairment by the International Federation of Multiple Sclerosis Societies in its Minimal Record of Disability for Multiple Sclerosis. We consider that the EDSS has important flaws that seriously limit its usefulness. In light of the widely accepted three-tier classification of dysfunction developed by the World Health Organization, the title is inappropriate. More substantial problems include inadequate precision in defining the degree of impairment in some functional categories of the scale, and the use of a mixture of neurologic signs elicited on examination and subjective information obtained from the patient in defining the overall scale. We suggest guidelines for developing a "Neurologic Impairment Scale" to rate impairment in MS.

Progressive multifocal leukoencephalopathy (PML): in vitro cell-mediated immune responses to mitogens and JC virus.

Cell-mediated immunity was studied by in vitro tests in seven patients with progressive multifocal leukoencephalopathy (PML). Lymphocyte proliferation in response to mitogenic stimulation was reduced to a variable degree in all patients, indicating a general impairment of cell-mediated immune responsiveness, although mitogen-induced production of the lymphokine migration inhibitory factor (LIF) was normal in most cases. Cell-mediated immunity to JC virus (JCV) was assessed by LIF production in response to JCV antigen. In the six PML patients tested, LIF production with JCV antigen was absent despite the presence of antibody to JCV in serum. This contrasted with positive LIF production in seropositive normal individuals and patients and patients with other diseases. These results provide the first in vitro evidence of a depressed cell-mediated immune response to JCV in patients with PML, and support the hypothesis that PML is accompanied by a selective marked deficiency in cellular response to this virus in association with a general depression of cell-mediated immunity of variable severity.

The indirect assay for leukocyte migration inhibitory factor (LIF)--standardization and the effect of pH.

In the indirect assay for leukocyte migration inhibitory factor (LIF), lymphokine-rich supernatants were obtained by culture of stimulated lymphocytes and then tested for LIF activity in agarose plates using purified granulocytes as target cells. Studies on the standardization of the conditions under which LIF acts on the target cells are described, with emphasis on the use of "standard" supernatants of known LIF activity and the influence of pH on the action of LIF and the sensitivity of the assay. The observation that LIF activity is reduced when the ambient pH falls below 7.2 is suggested as an explanation firstly for the "escape" phenomenon seen particularly in capillary tube assays for LIF, and secondly for the reduced sensitivity of the capillarly tube assay in comparison with the corresponding agarose plate assay.

Development of recombinant rabies viruses vectors with Gaussia luciferase reporter based on Chinese vaccine strain CTN181.

UNLABELLED: The recombinant rabies virus (RV) vectors encoding the secreted gene marker Gaussia luciferase (Gluc) were generated based on Chinese vaccine strain CTN181. Vectors included replication competent CTN-Gluc, CTN/G(Q333R)-Gluc, in which the amino acid in position 333 of glycoprotein was mutated from glutamine (Q) to arginine (R), and replication constrained CTNΔG-Gluc, in which the glycoprotein encoding gene (G) was deleted. The growth of recombinant RVs in transfected cells was confirmed through biochemical assays of Gluc activities. Gluc expression in recombinant CTNΔG-Gluc virus was highest while that in CTN/G(Q333R)-Gluc virus was lowest. The optimal time to harvest recombinant RVs was determined and the function of pathogenic and nonpathogenic rabies glycoprotein in virus recovery was examined. The addition of glycoprotein was slightly beneficial for virus recovery and the titer of rescued virus was lowered even when the amino acid in G333 position of glycoprotein was mutated from nonpathogenic Gln to pathogenic Arg. CONCLUSIONS: Viral vectors based on a human rabies vaccine strain CTN181 were successful. Gluc was useful as an in vitro gene marker for monitoring the growth of recombinant RVs iteratively in cell culture.

American Academy of Neurology (AAN) 60th Annual Meeting. 12 to 19 April 2008.

The Annual Meeting of the AAN is the major meeting in the USA covering all aspects of neurology and attracts a large number of international presenters. At the 2008 meeting in Chicago, as has been the case in recent years, multiple sclerosis (MS) was the neurological disorder that attracted the most extensive contributions and interest. Aspects of MS that were most actively addressed were trials of treatment with new agents (oral immune-modulating medications and monoclonal antibodies), further assessment of established immune-modulating agents particularly head-to-head trials, Devics disease (neuromyelitis optica) and its relationship to MS, and MS in children. In addition to about 300 poster and platform presentations on MS topics, MS therapy was reviewed at a 2-hour evening meeting. Space does not allow acknowledgement of most of the individual reports of particular interest and the following is a general overview.

Measurement of cerebrospinal fluid IgG in the diagnosis of multiple sclerosis.

CSF IgG was measured in 190 patients by Single Radial Immunodiffusion, A high value for the ratio CSF IgG/total protein (normal values being up to 14%) was obtained in 13 of 22 patients (54%) with definite or probable multiple sclerosis and in 16 of 137 patients (12%) with other neurological disorders excluding acute infections, subarachnoid haemorrhage and neurosyphilis. In 56 patients IgG and albumin were measured in CSF and serum using Rocket Immunoelectrophoresis (Electroimmunodiffusion) and results assessed by dividing the radio IgG/albumin in the CSF by the same ratio in the serum to obtain an Index. Because of the small number of normal patients, it was not possible to define a normal range but separation of patients with multiple sclerosis from those with other neurological disorders was even less clear-cut than with first method. Minor technical difficulties with the Rocket technique and prolonged storage of some of the specimens may at least partly explain the discouraging results with this method. It was concluded that the measurement of CSF IgG was of limited value to a clinican attempting to make a diagnosis in an individual patient with neurological disease.

Infarction of the conus medullaris.

We describe 5 patients who presented with an acute cauda equina syndrome, which we believe was due to infarction of the conus medullaris. In 3 patients, the onset was spontaneous, and in 2 patients it was secondary to temporary occlusion of the distal aorta during medical manipulation. Pain in the buttocks and posterior thighs was a prominent initial symptom in the 3 patients with unprovoked attacks. The main clinical features were profound impairment of bowel and bladder function and of perianal and perineal sensation (S3 to S5 segments). There was sensory and motor impairment in the legs of variable extent, most marked in the S1 and S2 segments, but extending as high as L4 in 2 patients. In 1 patient, ischemic changes in the conus medullaris were confirmed post mortem. Ischemia confined to the caudal tip of the spinal cord is rare, and an underlying anomaly of the pattern of arterial supply is a likely predisposing factor. Four patients had partial return of function over a period of weeks.

Chronic meningitis without predisposing illness--a review of 83 cases.

Eighty-three previously healthy patients with chronic meningitis presenting to a general hospital were reviewed. The single most common cause was tuberculosis (40 per cent) with cryptococcosis (7 per cent), malignancy (8 per cent) and other definable causes much less frequent. In one-third of patients (34 per cent) no cause was found although most appeared to respond to treatment either with anti-tuberculosis drugs or steroids. There were some differences in clinical presentation, the clinical picture being most characteristic in tuberculous meningitis and malignant meningitis. However, there were frequent exceptions to any general rule and, particularly in adults, the clinical features and changes in cell count, protein and glucose in the cerebrospinal fluid (CSF) did not reliably distinguish one form of chronic meningitis from another. Cerebral and meningeal biopsy produced disappointing results with respect to practical guidance in management. It is often necessary to begin treatment before a cause has been identified. Important points in management include the early use of anti-tuberculosis treatment and the difficulty in deciding on a trial of treatment with corticosteroids or amphotericin B. Not emphasised in previous reports is a subgroup of patients with idiopathic chronic meningitis who are responsive to treatment with steroids. Those patients tend to follow a more prolonged indolent course and often require long-term immunosuppression to control symptoms.

The crossed upgoing toe sign: a clinical study.

We compared the crossed upgoing toe sign with the plantar response as an indicator of pyramidal tract dysfunction in 125 normal subjects and 192 patients with neurological disorders. A positive crossed upgoing toe sign was associated significantly with a partial pyramidal tract lesion in the contralateral cerebral hemisphere with a frequency similar to that of Babinski's sign. Unlike Babinski's sign, however, the positive crossed upgoing toe sign was lost when pyramidal weakness was severe enough to produce paralysis of voluntary dorsiflexion of the great toe, and it was found only rarely with pyramidal tract lesions of the spinal cord. The crossed upgoing toe sign has little value as a sensitive indicator of a pyramidal tract lesion. It is potentially of limited value as an aid in determining the level of a pyramidal tract lesion (cerebral hemisphere versus spinal cord), but its usefulness is seriously impaired by the high frequency of false positive signs in normal subjects and patients with other neurological disorders.

A sensitive silver stain for proteins in agarose gels.

A silver stain for proteins in agarose gels which is at least 10 times as sensitive as Coomassie blue is described. The method is simple to use and is particularly useful for the study of protein bands in the gamma region on electrophoresis of fluids such as cerebrospinal fluid in which the protein concentration is low. It readily detects bands of IgG containing 20 to 40 ng/band (approx 3 to 6 ng of IgG/mm2 of gel).